An important factor in the production of dental caries is the periodic attack on the tooth surface by large amounts of acid produced by the microorganisms of the plaque. Research is proposed to study the production of acid by two oral microorganisms, Veillonella alcalescens and Arachnia propionica. The project will focus on the optimal growth conditions for production of acid and the enzymatic mechanisms by which the major metabolic end products, propionic and acetic acids, are formed. Although the overall pathways will be considered, special attention will be given to the enzymes involved with CO2 fixation and those enzymes directly concerned with the production of propionic acid. In the Veillonella, this involves a study of the biotin enzyme, methylmalonyl- COA decarboxylase, which has not been studied thoroughly. Studies will include techniques for the inhibition of acid production in these microorganisms both by chemical means and by utilization of endogenous control mechanisms, e.g. enzyme repression. A study of acid production and enzyme content will also be made with mixed cultures of these organisms, to look for any symbiotic relationships.